The Neuroscience of the Spotless Mind

Although there are undoubtedly even more Valentine’s Day-themed films than there are Shades of Grey, Eternal Sunshine of the Spotless Mind stands a cut above the rest. I say this not only as a movie-enthusiast but also as a neuroscience-enthusiast. This film may not be overtly about neuroscience, but it touches on questions and themes that are remarkably relevant to the scientific study of the brain.

Hmmm, brain scanning in the snow?

Eternal Sunshine is a difficult film to categorize; it is part romance, part drama, part comedy, and some even say part “sci-fi”. However, it fits well with our Valentine’s week because it is, in large part, a love story between Joel (Jim Carrey) and Clementine (Kate Winslet). The film even begins on Valentine’s Day, which Joel aptly describes in the opening line as “a holiday invented by greeting card companies to make people feel like crap”. In fact, it is on Valentine’s Day that he meets Clementine, and from there we embark on a wild ride through Joel and Clementine’s relationship that’s almost as convoluted as the brain itself.

Once we learn that the film is being told largely through Joel’s memories of their past relationship, the film shifts from a traditional rom-com to something much more complicated and provocative. Joel learns that Clementine has had him “erased” from her memory by a company called Lacuna, Inc. (Interestingly, “Lacuna” literally means an unfilled space or gap, and “lacunar amnesia” is used to describe loss of memory about a particular event). Although the exact methods utilized by Lacuna, Inc. are pure fiction (for instance, the “brain machine”, pictured here, generates brain images that look like fMRI scans yet is drastically different from a modern MRI scanner), what is interesting about the film is what it gets right. First, its portrayal of memory as a biological phenomenon that is highly malleable and susceptible to manipulation has proven surprisingly accurate, and second, it hits on some fundamental principles of emotional memories that have a true neurological basis.

“Spotless” rats, mice…and even humans?

Learning and memory has been a hot topic of neuroscience research throughout the last couple of decades. By the time Eternal Sunshine was released in 2004, our understanding of memory had undergone some important transformations. Most relevant to the film, the “reconsolidation” hypothesis of memory retrieval, which is the idea that a retrieved memory is made fragile and must be re-stored in the brain as long-term memory, was gaining significant traction. In 2000, Nader et al. demonstrated convincingly that protein synthesis in the amygdala (a region of the brain strongly implicated in fear conditioning, a basic form of learning and memory) was required for the reconsolidation of fear memories in rats [1]. In other words, retrieving a memory renders it susceptible to disruption, and protein synthesis is necessary for reconsolidating it into long-term memory (read about this study and more on false memories in a previous NeuWrite post!). As author and blogger Steven Johnson points out, it is vaguely possible that the basic procedure in Eternal Sunshine could be similarly taking advantage of memories’ vulnerability during retrieval in order to target them for erasure [2].

However, this experiment was performed in rats and their “memories” were merely conditioned fear responses: so what about emotional long-term memories in humans? Remarkably, Kroes and colleagues (2014) recently provided early evidence for the reconsolidation hypothesis in humans as well [3]. Unipolar-depressive patients were shown emotionally-arousing stories in a slideshow, and one week later they were asked to remember one of those stories. Patients who were subsequently given anesthesia and electroconvulsive therapy (ECT: electrical stimulation applied to the cranium to elicit short-lived seizure activity in the brain) were later unable to remember the story that they had retrieved prior to ECT. In contrast, their memories for the non-retrieved stories were unimpaired. This corroborates the hypothesis that memory retrieval is followed by a period in which it must be reconsolidated into long-term memory, and disrupted reconsolidation renders the memory susceptible to manipulation and even erasure. Although it is unlikely that an approach such as this will ever become mainstream enough that a company along the vein of Lacuna, Inc. would be sustainable (I don’t envision people rushing off to be anesthetized and electro-shocked after every break-up, but who knows?), other researchers have experimented with pharmacological interventions [4] and non-invasive behavioral training [5] with similar results. The possibility of disrupting negative emotional memories has significant clinical implications, such as for patients who suffer from post-traumatic stress disorder.

However, if you have actually seen Eternal Sunshine, you may have noticed that the Lacuna, Inc. tech named Stan (played by Mark Ruffalo) erases Joel’s memories by finding little splashes of activity in his brain and zapping them with a click of his mouse. Here, Stan seems to have located and targeted the engrams – the specific neurological signatures – of Joel’s memories of Clementine. Although the existence and specificity of engrams is still an area of ongoing exploration, a study out of Susumu Tonegawa’s lab at MIT got a lot of press (with flashy titles such as “Eternal sunshine of the spotless mouse”) this past year when they were able to identify specific populations of neurons (engrams) in the mouse hippocampus that were associated with conditioned memories of fear or reward [6]. Using optogenetics, the researchers trained mice to avoid or approach certain areas of a box when fear- or reward-associated neuronal populations, respectively, were activated with light. Moreover, the researchers could make a memory engram associated with fear become associated with reward or vice versa, as indicated by a reversal in the mice’s behavior when those engrams were light-activated. Thus, the latest research in neuroscience is just beginning to push the ideas portrayed onscreen in Eternal Sunshine to the next level; perhaps instead of zapping Joel’s memories of Clementine away for good, Stan could change Joel’s emotional response to them.

After all, it isn’t the memories themselves that Joel and Clementine are each trying to escape when they erase each other from their lives; it’s the painful, heart-wrenching emotions that they elicit. Nevertheless, the emotional salience of those memories makes them resilient to total eradication, and once again, Eternal Sunshine touches on another fascinating area of neuroscience research with surprising validity.

Eternal Sunshine: Emotional memories and familiarity

While trying to memorize countries and their capitals in 9th grade Social Studies, my teacher encouraged us all to come up with mnemonics that were as inappropriate, offensive, or otherwise emotionally-arousing as possible. Not only was this an effective technique for engaging a bunch of 15-year-olds, but it is a strategy validated by research in psychology and increasingly in neuroscience. Emotional memories have been shown to hold a privileged place in long-term memory [7], and that certainly seems to be the case in Eternal Sunshine of the Spotless Mind.

Emotion provides an added dimension to our memories – another set of variables that Stan has to identify and wipe out in Joel’s brain in order to eradicate a memory. From a neurological perspective, the amygdala appears to be a key player in the emotional dimension of memory. For instance, patients with amygdalar damage do not demonstrate enhanced recall of emotional compared to non-emotional information, which is typical in the general population [8]. In fact, studies in both animals [9] and humans [7,10] suggest that the amygdala is important for both the formation and the retrieval of memories via its connections to many brain areas, such as the medial temporal lobe (which includes the hippocampus) [7].

The amygdala’s robust connections with the medial temporal lobe are of particular relevance to Eternal Sunshine. At the beginning of the film (which, SPOILER ALERT, takes place chronologically at the end) when the ex-lovers supposedly “meet”, Clementine asks insistently if she has seen Joel before. This is a classic example of familiarity without recollection. In fact, there are many instances in the film like this when characters who have had their memories erased demonstrate some degree of familiarity for people, places or things that they can’t outright recall. A fundamental distinction between familiarity and recollection has been posited by memory psychologists for many years, and this idea has gained some support from research in neuroscience as well. For instance, the perirhinal cortex (another subregion of the medial temporal lobe) is thought to be particularly important for familiarity, whereas the hippocampus is strongly implicated in memory recall (although these functions may not be entirely segregated [11]). Although the neural circuitry underlying familiarity and recollection of emotional memories is not fully understood, a relatively recent study found evidence of impaired familiarity but preserved recollection in rats following amygdala damage [12]. This is particularly interesting given the strong connections between the amygdala and both perirhinal cortex and hippocampus. Therefore, the amygdala may be especially important for aspects of memory pertaining to familiarity.

They don’t LOOK like they’re meeting for the first time…

Although more research is certainly needed on this topic, it provides a fascinating neurological backdrop to the memory erasure experienced by Joel and Clementine. To me, it gives a whole new meaning to Eternal Sunshine of the Spotless Mind. The human brain is immensely complicated, and rich, emotional memories are deeply intertwined into our brain’s neural circuitry. Perhaps this is what subconsciously drives Joel to jump on a train to Montauk – the place where he first met Clementine – on Valentines Day, miraculously bringing her back into his life. Lacuna, Inc. may have erased Joel and Clementine’s explicit memories for each other, but the brain (and, in the romantic spirit of Valentine’s, the heart) is not so easily beguiled. Thus, Eternal Sunshine concludes with resounding hopefulness, assuring us that the mind can never be truly “spotless”.